Lacidipine Ameliorates the Endothelial Senescence and Inflammatory Injury Through CXCR7/P38/C/EBP-β Signaling Pathway

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2021 Jul 23

PMID 34295928

Citations 4

Authors

Xing Liu

Zhuoshan Huang

Yuanyuan Zhang

Xing Shui

Fanmao Liu

Zhen Wu

Shiyue Xu

Affiliations

Soon will be listed here.

Abstract

Lacidipine, a third-generation calcium channel blocker, exerts beneficial effects on the endothelium of hypertensive patients in addition to blood pressure lowering. However, the detailed mechanism underlying Lacidipine-related endothelial protection is still elusive. Sixteen spontaneous hypertensive rats (SHRs) were randomly divided into two groups: Lacidipine-treated SHR group and saline-treated control group. Tail systolic blood pressure was monitored for four consecutive weeks. Endothelial cells (ECs) were pretreated with Lacidipine prior to being stimulated with HO, bleomycin, or Lipopolysaccharides (LPS) . Then, cell activity, migration, and senescence were measured by Cell Counting Kit-8 assay, transwell assay, and β-galactosidase staining, respectively. The fluorescent probe 2', 7'-dichlorofluorescein diacetate (DCFH-DA) was used to assess the intracellular reactive oxygen species (ROS). Related protein expression was detected by Western blotting and immunofluorescence. Our data showed that Lacidipine treatment lowered the blood pressure of SHRs accompanied by the elevation of CXCR7 expression and suppression of P38 and CCAAT/enhancer-binding protein beta (C/EBP-β) compared with the control group. experiments further demonstrated that Lacidipine increased the cell viability and function of ECs under oxidative stress, cell senescence, and inflammatory activation the CXCR7/P38/signaling pathway. Our results suggested that Lacidipine plays a protective role in EC senescence, oxidative stress, and inflammatory injury through the regulation of CXCR7/P38/C/EBP-β signaling pathway.

Citing Articles

[C/EBPβ mediates expressions of downstream inflammatory factors of the tumor necrosis factor- signaling pathway in renal tubular epithelial cells with knockdown].

Huang D, Liu Y, Li D, Zhang J, Yang Y, Sun L Nan Fang Yi Ke Da Xue Xue Bao. 2024; 44(1):156-165.

PMID: 38293987 PMC: 10878891. DOI: 10.12122/j.issn.1673-4254.2024.01.18.

Role of Oxidative Stress-Dependent C/EBPβ Expression on CAF Transformation Inducing HCT116 Colorectal Cancer Cell Progression; Migration and Invasion.

Hassametto A, Tanomrat R, Muangthong T, Worawichawong S, Suwannalert P Asian Pac J Cancer Prev. 2023; 24(11):3825-3835.

PMID: 38019240 PMC: 10772768. DOI: 10.31557/APJCP.2023.24.11.3825.

Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis.

Jimenez-Dinamarca I, Prado Y, Tapia P, Gatica S, Alt C, Lin C Biol Res. 2023; 56(1):8.

PMID: 36869357 PMC: 9983216. DOI: 10.1186/s40659-023-00419-4.

Alveolar type 2 epithelial cell senescence and radiation-induced pulmonary fibrosis.

Zhou S, Zhu J, Zhou P, Gu Y Front Cell Dev Biol. 2022; 10:999600.

PMID: 36407111 PMC: 9666897. DOI: 10.3389/fcell.2022.999600.

References

Chakraborty S, Liu L, Fitzsimmons L, Porwollik S, Kim J, Desai P . Glycolytic reprograming in Salmonella counters NOX2-mediated dissipation of ΔpH. Nat Commun. 2020; 11(1):1783. PMC: 7156505. DOI: 10.1038/s41467-020-15604-2. View

Sierro F, Biben C, Martinez-Munoz L, Mellado M, Ransohoff R, Li M . Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7. Proc Natl Acad Sci U S A. 2007; 104(37):14759-64. PMC: 1976222. DOI: 10.1073/pnas.0702229104. View

Park J, Ahn J, Lee T, Park C, Kim B, Lee J . Laminarin Pretreatment Provides Neuroprotection against Forebrain Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Neuroinflammation in Aged Gerbils. Mar Drugs. 2020; 18(4). PMC: 7230782. DOI: 10.3390/md18040213. View

Canovas B, Nebreda A . Diversity and versatility of p38 kinase signalling in health and disease. Nat Rev Mol Cell Biol. 2021; 22(5):346-366. PMC: 7838852. DOI: 10.1038/s41580-020-00322-w. View

Suleyman H, Halici Z, Hacimuftuoglu A, Gocer F . Role of adrenal gland hormones in antiinflammatory effect of calcium channel blockers. Pharmacol Rep. 2006; 58(5):692-9. View

Zhao Y, Tan Y, Xi S, Li Y, Li C, Cui J . A novel mechanism by which SDF-1β protects cardiac cells from palmitate-induced endoplasmic reticulum stress and apoptosis via CXCR7 and AMPK/p38 MAPK-mediated interleukin-6 generation. Diabetes. 2013; 62(7):2545-58. PMC: 3712029. DOI: 10.2337/db12-1233. View

Jain S, Li Y, Patil S, Kumar A . A single-nucleotide polymorphism in human angiotensinogen gene is associated with essential hypertension and affects glucocorticoid induced promoter activity. J Mol Med (Berl). 2005; 83(2):121-31. DOI: 10.1007/s00109-004-0621-5. View

Taddei S, Virdis A, Ghiadoni L, Uleri S, Magagna A, Salvetti A . Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients. Hypertension. 1997; 30(6):1606-12. DOI: 10.1161/01.hyp.30.6.1606. View

Bai B, Yang Y, Wang Q, Li M, Tian C, Liu Y . NLRP3 inflammasome in endothelial dysfunction. Cell Death Dis. 2020; 11(9):776. PMC: 7501262. DOI: 10.1038/s41419-020-02985-x. View

10.

Thomas F, Rudnichi A, Bacri A, Bean K, Guize L, Benetos A . Cardiovascular mortality in hypertensive men according to presence of associated risk factors. Hypertension. 2001; 37(5):1256-61. DOI: 10.1161/01.hyp.37.5.1256. View

11.

Wang J, Su C, Wang Y, Huang Y, Yang Z, Chen L . Elevated circulating endothelial microparticles and brachial-ankle pulse wave velocity in well-controlled hypertensive patients. J Hum Hypertens. 2008; 23(5):307-15. DOI: 10.1038/jhh.2008.137. View

12.

Higashi Y, Kihara Y, Noma K . Endothelial dysfunction and hypertension in aging. Hypertens Res. 2012; 35(11):1039-47. DOI: 10.1038/hr.2012.138. View

13.

Park B, Kook S, Lee S, Jeong J, Brufsky A, Lee B . An isoform of C/EBPβ, LIP, regulates expression of the chemokine receptor CXCR4 and modulates breast cancer cell migration. J Biol Chem. 2013; 288(40):28656-67. PMC: 3789964. DOI: 10.1074/jbc.M113.509505. View

14.

Krenek P, Salomone S, Kyselovic J, Wibo M, Morel N, GODFRAIND T . Lacidipine prevents endothelial dysfunction in salt-loaded stroke-prone hypertensive rats. Hypertension. 2001; 37(4):1124-8. DOI: 10.1161/01.hyp.37.4.1124. View

15.

Rao K, Shen X, Pardue S, Krzywanski D . Nicotinamide nucleotide transhydrogenase (NNT) regulates mitochondrial ROS and endothelial dysfunction in response to angiotensin II. Redox Biol. 2020; 36:101650. PMC: 7408723. DOI: 10.1016/j.redox.2020.101650. View

16.

Liu Y, Yin H, Li C, Jiang F, Zhang S, Zhang X . Sinapine Thiocyanate Ameliorates Vascular Endothelial Dysfunction in Hypertension by Inhibiting Activation of the NLRP3 Inflammasome. Front Pharmacol. 2021; 11:620159. PMC: 7901921. DOI: 10.3389/fphar.2020.620159. View

17.

Stefanatos R, Sanz A . The role of mitochondrial ROS in the aging brain. FEBS Lett. 2017; 592(5):743-758. DOI: 10.1002/1873-3468.12902. View

18.

Yang Y, Zhou Y, Wang Y, Wei X, Wu L, Wang T . Exendin-4 reverses high glucose-induced endothelial progenitor cell dysfunction via SDF-1β/CXCR7-AMPK/p38-MAPK/IL-6 axis. Acta Diabetol. 2020; 57(11):1315-1326. DOI: 10.1007/s00592-020-01551-3. View

19.

Dai X, Tan Y, Cai S, Xiong X, Wang L, Ye Q . The role of CXCR7 on the adhesion, proliferation and angiogenesis of endothelial progenitor cells. J Cell Mol Med. 2011; 15(6):1299-309. PMC: 4373330. DOI: 10.1111/j.1582-4934.2011.01301.x. View

20.

Oeseburg H, de Boer R, Buikema H, van der Harst P, van Gilst W, Sillje H . Glucagon-like peptide 1 prevents reactive oxygen species-induced endothelial cell senescence through the activation of protein kinase A. Arterioscler Thromb Vasc Biol. 2010; 30(7):1407-14. DOI: 10.1161/ATVBAHA.110.206425. View